Hypokalemia, polyuria, hypernatremia and overproduction of renal prostaglandins characterize prolonged treatment of dogs with desoxycorticosterone. The present studies indicate that the hypernatremia is associated with an increase in plasma arginine vasopressin despite a tendency for the osmotic threshold for vasopressin release to increase. The polyuria thus develops despite increases in plasma vasopressin and is unaffected by a further increase in plasma vasopressin produced by treatment with vasopressin. Treatment with indomethacin which corrects the overproduction of renal prostaglandins restores renal responsiveness to vasopressin and thereby corrects the polyuria, hypernatremia, and increased secretion of vasopressin. These findings suggest that in disorders such as primary aldosteronism, hypokalemia, hypernatremia and polyuria may be associated with an increase in circulating vasopressin and this may be a factor in the hypertension.